CNS Pharmacology

1. CNS Pharmacology Manar Zraikat PHD

2. Neurotransmitters Chemical substances responsible for the chemical communication across synapses and other neuro-effector junctions. Act by causing changes in the ionic conductivity of the membrane and consequent shifts in membrane potentials. May also be found in plants and microorganisms.

3. Neurotransmitters Steps of Neurotransmittion: • Regional distribution and localization • Synthesis • Storage • Release • Termination of action • Reproducibility of action

4. Neurotransmitters Immunohistochemistry refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues Histochemical refers the chemistry of tissues Microiontophoresis is a process for observing or recording the effect of an ionized substance on nerve cells that involves inserting a double micropipette into the brain close to a nerve cell, injecting an ionized fluid through one barrel of the pipette, and using a concentrated saline solution in the other tube as an electrical conductor to pick up and transmit back to an oscilloscope any change in neural activity How to Study: By • Histochemical fluorescence. • Immunohistochemical studies. • Concentration of agents in sections • Microiontophoresis • Pharmacodynamic studies. • Receptor studies.

5. Amino Acid Neurotransmitters An amino acid neurotransmitter is an amino acid which is able to transmit a nerve message across a synapse

6. biogenic amines Neurotransmitters These neurotransmitters act at both neurons and muscles to affect various processes such as egg laying learning. 

8. Neurohormones Are hormones arising from neurons. Include any hormone produced and released by neuroendocrine cells into the blood. Because they are hormones, they are secreted into the circulation for systemic effect, but they can also have a role of neurotransmitter

9. Neuromodulators Substances that can influence neuronal activity differently than neurotransmitters. They originate from cellular and nonsynaptic sites Such as CO2, NH4, steroids influence the general level of neuronal excitability without altering the membrane potential.

10. Neuromediators Substances that participate in the elicitation of postsynaptic response to a neurotransmitter or a modulator ( e.g. cAMP, cGMP).

11. Factors Affecting Intensity and Duration of CNS Drugs Concentration in blood. Blood Brain Barrier (BBB). Receptor binding. Storage of the transmitter.

12. Local Anesthesia Defined as any technique used to induce the absence of sensation in a specific part of the body A local anesthetic is a drug that causes reversible local anesthesia and a loss of sensation at a local area

13. History • Cocaine is a naturally occurring compound. It was the first anesthetic to be discovered and is the only naturally occurring local anesthetic; all others are synthetically derived. • Sigmund Freud, the noted Austrian psychoanalyst, used cocaine on his patients and became addicted through self-experimentation. • In the 1880s, Koller introduced cocaine to the field of ophthalmology, and Hall introduced it to dentistry. • Halsted was the first to report the use of cocaine for nerve blocks in the United States in 1885 • Procaine, the first synthetic derivative of cocaine, was developed in 1904. • Lofgren later developed lidocaine, the most widely used cocaine derivative, during World War II in 1943.

14. Features of an Ideal Local Anesthetic Rapid onset Non irritating. Sufficient duration of action Reversible effect. Low systemic toxicity. Proper physical properties: Stability Water solubility.

15. Paths of local anesthetic (LA) to receptor sites. • Extracellular anesthetic exists in equilibrium between charged and uncharged forms. • The charged cation penetrates lipid membranes poorly; intracellular access is thus achieved by passage of the uncharged form. • Intracellular re-equilibration results in formation of the more active charged species, which binds to the receptor at the inner vestibule of the sodium channel.

16. Chemistry of Local Anesthesia Amides Esters

17. Esters • Cocaine • Benzocaine: usually topical use. • Chloroprocaine • Tetracaine

18. Amides • Lidocaine: Most commonly used. • Because Rapid onset, Most intense, Long duration. • Bupivacaine: used in obstetrics because of its longer duration (24hrs). • Levobupivacaine • Ropivacaine • Etidocaine • Mepivacaine • Prilocaine

19. Routes of Administration of Local Anesthesia • Topical or Surface: Lidocaine and Tetracaine • Infiltration: Most LAs • Regional Block: • Nerve Block: most LAs • Spinal(Subarachnoid): Lidocaine, Tetracaine • Lumbar Epidural: Lidocaine, Bupivacaine • cuadral • Intravenous Extremity Block: Lidocaine, Tetracaine • Systemic: Intravenous: Lidocaine, Procain • Oral

20. Peak blood levels of anesthetic agents following administration into various anatomic sites The intercostal space (ICS) is the anatomic space between two ribs Caudal near the tail or the posterior part of the body Epidural administration is a medical route of administration in which a drug or contrast agent is injected into the epidural space of the spinal cord The brachial plexus is a network of nerves, running from the spine, and passes through thecervicoaxillary canal in the neck The femoral nerve is a nerve in the thigh that supplies skin on the upper thigh and inner leg